Phospholipase A.sub.2 is an enzyme which hydrolyzes .beta.-ester bonds in phospholipid to give fatty acids and lysophospho-lipids. Especially, it releases arachidonic acid which can be a precursor of prostaglandins, leukotriene, thromboxane and the like from membrane phospholipids and is thought to play an important role in the production of these inflammatory mediators. In recent years, phospholipase A.sub.2 has been purified from the inflammatory sites of human inflammatory diseases and inflammatory model animals (it will be called phospholipase A.sub.2 from inflammatory sites) and its properties have been clarified. This enzyme is thought to have the action to accelerate the inflammatory reactions, therefore the drug to inhibit the activity of this enzyme can be expected to reveal anti-inflammatory actions.
Complement C3 is a protein which has been known to perform the key functions in the complement pathway. C3 is hydrolyzed stepwise by a protease in blood. In other words, it is cleaved first with convertase into C3a an dC3b. C3b binds through its thiol ester site to the surface of activators followed by activation of the complement pathway to form a membrane attack complex. C3a works as an anaphylatoxin. At this time, a minor part of C3b binds to the activators, while the major part reacts with water to lose the binding activity, further undergoes hydrolysis by a protease to convert into C3dg or C3d finally.
The present inventors have already applied for patents after finding that human and rat C3dg inhibit specifically phospholipase A.sub.2 purified from inflammation sites, succeeding in expression of rat C3 cDNA in Escherichia coli to produce a part of rat C3.alpha. chain (containing the C3dg part) as a recombinant protein, and realizing that the recombinant protein inhibits specifically phospholipase A.sub.2 purified from inflammatory sites (PCT/J90/00996, W091/01999).
Human C3dg is, however, a protein of about 39 kDa molecular weight and it can be anticipated that the use of said protein as an anti-inflammatory as such will cause troubles in, for example, the transference to the affected part, the storage stability or antigenicity.
Thus, a novel peptide having inhibitory activity against phospholipase A.sub.2 from inflammatory sites is desirably provided as an anti-inflammatory without such troubles.
Hereupon, the present inventors have made intensified studies in order to solve the above-mentioned problems to find that a part of the amino acid sequence of C3dg has action to inhibit phospholipase A.sub.2, and attained the present invention.